The research focuses on the mechanism by which Abelson murine leukemia virus (Ab-MLV) induces lymphomas and transforms lymphoid cells. The role of Abl in triggering growth, suppressing apoptosis and driving the selection of tumor suppressor mutations in Tp53 and Mts1 will be examined. Four specific aims will addressed. The first examines the selection of Tp53 mutations, including the type of mutations, the kinetics at which they arise and the forces that drive their selection. The second specific aim studies the altered expression of p16 protein in vivo and in vitro, as it relates to Ab-MLV mediated transformation. The third specific aim utilizes a recently discovered Ab-MLV mutant which does not stimulate growth but does suppress apoptosis. This mutant leads to changes in the Bcl-x protein and altered cleavage of PARP, a substrate for the ICE proteases. The pathways by which v-Abl induces these signals and suppresses apoptosis will be examined. The last specific aim studies the mechanism by which v-Abl disrupts control of G1 transit.